Association between TLR4 (+896A/G and +1196C/T) Polymorphisms and Gastric Cancer Risk: An Updated Meta-Analysis

Background

Toll-like receptor 4 (TLR4) is a receptor of lipopolysaccharide in the signaling transduction of gastric epithelial cell. It plays a pivotal role in activation of innate immunity and pathogen recognition and thus acts as a modulator in the development and progression of gastric cancer. Growing studies explored the association of polymorphisms in TLR4 with susceptibility to gastric cancer, but the results have remained controversial and conflicting. To investigate the effect of two selected TLR4 (+896A/G and +1196C/T) polymorphisms on gastric cancer, we performed a meta-analysis.

Methods

A comprehensive search was conducted to identify all eligible case-control publications investigating the association between TLR4 polymorphisms and gastric cancer risk. Odds ratios (OR) and corresponding 95% confidence intervals (CI) were used to assess such association.

Results

Up to March 26 2014, 10 published case-control studies from PubMed and EMBase were available, involving a total of 1888 gastric cancer patients and 3433 control subjects. In the overall meta-analyses, a significantly increased gastric cancer risk was detected in TLR4 +896A/G polymorphism (heterozygous model, AG vs. AA: OR = 1.67, 95% CI, 1.39–2.01; additive model, G vs. A: OR = 1.64, 95% CI, 1.37–1.95) and TLR4 +1196C/T polymorphism (heterozygous model, CT vs. CC: OR = 1.42, 95% CI, 1.11–1.81; additive model, T vs. C: OR = 1.36, 95% CI, 1.08–1.72), similar results were obtained in the subgroup analyses of Caucasian, whereas no associations were detected in any genetic models of non-Caucasian.

Conclusions

The overall results suggest that TLR4 polymorphisms (+896A/G and +1196C/T) may be associated with a significantly increased gastric cancer risk in Caucasian.     

Red and Processed Meat Intake Is Associated with Higher Gastric Cancer Risk: A Meta-Analysis of Epidemiological Observational Studies

Background

Red and processed meat was concluded as a limited-suggestive risk factor of gastric cancer by the World Cancer Research Fund. However, recent epidemiological studies have yielded inconclusive results.

Methods

We searched Medline, EMBASE, and the Cochrane Library from their inception to April 2013 for both cohort and case-control studies which assessed the association between red and/or processed meat intake and gastric cancer risk. Study-specific relative risk estimates were polled by random-effect or fixed-effect models.

Results

Twelve cohort and thirty case-control studies were included in the meta-analysis. Significant associations were found between both red (RR: 1.45, 95% CI: 1.22–1.73) and processed (RR: 1.45, 95% CI: 1.26–1.65) meat intake and gastric cancer risk generally. Positive findings were also existed in the items of beef (RR: 1.28, 95% CI: 1.04–1.57), bacon (RR: 1.37, 95% CI: 1.17–1.61), ham (RR: 1.44, 95% CI: 1.00–2.06), and sausage (RR: 1.33, 95% CI: 1.16–1.52). When conducted by study design, the association was significant in case-control studies (RR: 1.63, 95% CI: 1.33–1.99) but not in cohort studies (RR: 1.02, 95% CI: 0.90–1.17) for red meat. Increased relative risks were seen in high-quality, adenocarcinoma, cardia and European-population studies for red meat. And most subgroup analysis confirmed the significant association between processed meat intake and gastric cancer risk.

Conclusions

Our findings indicate that consumption of red and/or processed meat contributes to increased gastric cancer risk. However, further investigation is needed to confirm the association, especially for red meat.     

Vitamin A Intake and Risk of Melanoma: A Meta-Analysis

Background

Mounting evidence from experimental and animal studies suggests that vitamin A may have a protective effect on melanoma, but the findings on the association of vitamin A intake with risk of melanoma have been inconsistently reported in epidemiologic studies. We attempted to elucidate the association by performing a meta-analysis.

Methods

Eligible studies were identified by searching PubMed and EMBASE databases, as well as by reviewing the references of retrieved publications. Summary odds ratios (OR) with corresponding 95% confidence interval (CI) were computed with a random-effects model. Study-specific ORs and 95% CIs for the highest vs. lowest categories of vitamin A intake were pooled.

Results

A total of 8 case-control studies and 2 prospective studies comprising 3,328 melanoma cases and 233,295 non-case subjects were included. The summary OR for the highest compared with the lowest intake of total vitamin A, retinol and beta-carotene was 0.86 (95% CI = 0.59–1.25), 0.80 (95% CI = 0.69–0.92) and 0.87 (95%CI = 0.62–1.20), respectively. Significant heterogeneity was observed among studies on vitamin A and beta-carotene intake, but not among studies on retinol intake. Subgroup and sensitivity analyses confirmed these findings. There was no indication of publication bias.

Conclusion

Findings from this meta-analysis suggest that intake of retinol, rather than of total vitamin A or beta-carotene, is significantly associated with reduced risk of melanoma.     

Diabetes Mellitus as a Risk Factor for Open-Angle Glaucoma: A Systematic Review and Meta-Analysis

Objective

To determine the association between diabetes mellitus (DM) and primary open-angle glaucoma (POAG).

Methods

This is a systematic review and meta-analysis of case-control and cohort studies. The literature search included two databases (PubMed and Embase) and the reference lists of the retrieved studies. Separate meta-analyses for case-control studies and cohort studies were conducted using random-effects models, with results reported as adjusted odds ratios (ORs) and relative risks (RRs), respectively.

Results

Thirteen studies—seven case-control studies and six population-based cohort studies—were included in this meta-analysis. The pooled RR of the association between DM and POAG based on the risk estimates of the six cohort studies was 1.40 (95% CI, 1.25–1.57). The pooled OR of the association between DM and POAG based on the risk estimates of the seven case-control studies was 1.49 (95% CI, 1.17–1.88). There was considerable heterogeneity among the case-control studies that reported an association between DM mellitus and POAG (P<0.001) and no significant heterogeneity among the cohort studies (P = 0.377). After omitting the case-control study that contributed significantly to the heterogeneity, the pooled OR for the association between DM and POAG was 1.35 (95% CI, 1.06–1.74).

Conclusions

Individuals with DM have an increased risk of developing POAG.     

Reported High Salt Intake Is Associated with Increased Prevalence of Abdominal Aortic Aneurysm and Larger Aortic Diameter in Older Men

Background

Salt intake has been implicated in the pathogenesis of abdominal aortic aneurysm (AAA) through studies in rodent models but not previously studied in humans. The aim of this study was to examine the association between reported addition of salt to food and the prevalence of AAA.

Methods

A risk factor questionnaire which contained a question about salt intake was included as part of a population screening study for AAA in 11742 older men. AAA presence was assessed by abdominal ultrasound imaging using a reproducible protocol.

Results

The prevalence of AAA was 6.9, 8.5 and 8.6% in men who reported adding salt to food never, sometimes and always, respectively, p = 0.005. Addition of salt to food sometimes (odds ratio [OR]: 1.22, 95% confidence interval [CI]: 1.03–1.44) or always (OR: 1.23, 95% CI 1.04–1.47) was independently associated with AAA after adjustment for other risk factors including age, waist-hip ratio, blood pressure, history of hypertension, high cholesterol, angina, diabetes, myocardial infarction and stroke. Salt intake was also independently associated with aortic diameter (beta 0.023, p = 0.012). In men with no prior history of hypertension, high cholesterol, angina, myocardial infarction or stroke (n = 4185), the association between addition of salt to food sometimes (OR: 1.41, 95% CI 0.96–2.08) or always (OR: 1.52, 95% CI 1.04–2.22) and AAA remained evident.

Conclusion

Reported salt intake is associated with AAA in older men. Additional studies are needed to determine whether reducing salt intake would protect against AAA.     

Tea Consumption and Risk of Head and Neck Cancer

Background

The current study evaluated the association between tea consumption and head and neck cancer (HNC) in Taiwan, where tea is a major agricultural product and a popular beverage.

Methods

Interviews regarding tea consumption (frequency, duration, and types) were conducted with 396 HNC cases and 413 controls. Unconditional logistic regression was performed to estimate the odds ratio (OR) and 95% confidence interval (CI) of HNC risk associated with tea drinking, adjusted for sex, age, education, cigarette smoking, betel quid chewing, and alcohol drinking.

Results

A reduced HNC risk associated with tea drinking (OR for every cup per day = 0.96, 95% CI: 0.93–0.99; OR for ≧5 cups per day = 0.60, 95% CI: 0.39–0.94) was observed. The association was especially significant for pharyngeal cancer (OR for every cup per day = 0.93, 95% CI: 0.88–0.98; OR for ≧5 cups per day = 0.32, 95% CI: 0.16–0.66). A significant inverse association between HNC and tea consumption was observed particularly for green tea.

Conclusions

This study suggests that tea drinking may reduce the risk of HNC. The anticancer property of tea, if proven, may offer a natural chemopreventive measure to reduce the occurrence of HNC.     

Relationship between Rad51 G135C and G172T Variants and the Susceptibility to Cancer: A Meta-Analysis Involving 54 Case-Control Studies

Background

The associations between Rad51 gene polymorphisms (G135C and G172T) and risk of cancer have been investigated, but the results were inconclusive. To get a comprehensive evaluation of the association above, we performed a meta-analysis of published studies.

Methods

A computerized search of PubMed, Embase and Web of Knowledge databases for all relevant studies was performed and the data were analyzed in a meta-analysis. The overall odds ratio (OR) with the 95% confidence interval (95% CI) was calculated to assess the strength of the association between Rad51 polymorphisms and cancer risk. Data were analyzed using fixed- or random-effects model when appropriate. Sensitivity analysis and publication bias test were also estimated.

Results

Overall, a total of 54 case-control studies were included in the current meta-analysis, among which 42 studies with 19,142 cases and 20,363 controls for RAD51 G135C polymorphism and 12 studies with 6,646 cases and 6,783 controls for G172T polymorphism. For G135C polymorphism, the pooled results indicated that significantly increased risk was found in overall cancers (homozygote model: OR = 1.776, 95% CI = 1.288–2.449; allelic genetic model: OR = 1.169, 95% CI = 1.016–1.345; recessive model: OR = 1.946, 95% CI = 1.336–2.835), especially in breast cancer (homozygote model: OR = 1.498, 95% CI = 1.026–2.189; recessive model: OR = 1.732, 95% CI  =  1.170–2.562). For G172T polymorphism, a decreased cancer risk was observed in head and neck cancer (homozygote model: OR  =  0.621, 95% CI  =  0.460–0.837; allelic genetic model: OR  =  0.824, 95% CI  =  0.716–0.948; recessive model: OR  =  0.639, 95% CI = 0.488–0.837).

Conclusions

Our results suggested that the Rad51 G135C polymorphism is a candidate for susceptibility to overall cancers, especially to breast cancer, and that the Rad51 G172T might play a protective role in the development of head and neck cancer.     

Genetic Polymorphism in PDE4D Gene and Risk of Ischemic Stroke in Chinese Population: A Meta-Analysis

Background

Stroke is the second most common cause of death and major cause of disability worldwide. The SNP 83 in PDE4D gene has been suggested as a risk factor in ischemic stroke, but direct evidence from genetic association studies remains inconclusive even in Chinese population.

Methods

Meta-analysis of case-control studies on the relationship between SNP 83 in PDE4D gene and susceptibility to ischemic stroke in Chinese population published domestically and abroad from January 2003 to September 2012.

Results

9 case-control studies were selected. Meta-analysis results showed that the significant association between SNP 83 and ischemic stroke was found under the dominant model (OR = 1.34, 95% CI: 1.20–1.49) and recessive model (OR = 1.45, 95% CI: 1.19–1.76) in Chinese population. In subgroup meta-analysis, SNP 83 and atherothrombotic stroke, rather than lacunar stroke, showed the significant association under the dominant model (OR = 1.69, 95% CI: 1.41–2.01) and recessive model (OR = 1.47, 95% CI: 1.04–2.06).

Conclusions

The results suggest that SNP 83 in PDE4D gene is significantly associated with susceptibility to ischemic stroke in Chinese population.     

CYP2E1 RsaI/PstI Polymorphism and Gastric Cancer Susceptibility: Meta-Analyses Based on 24 Case-Control Studies

Background

Previous reports implicate CYP2E1 RsaI/PstI polymorphism as a possible risk factor for several cancers. Published studies on the relationship of CYP2E1 RsaI/PstI polymorphisms with the susceptibility to gastric cancer are controversial. This study aimed to determine this relationship accurately.

Methods

Meta-analyses that assessed the association of CYP2E1 RsaI/PstI variations with gastric cancer were conducted. Subgroup analyses on ethnicity, smoking status, alcohol consumption, and source of controls were also performed. Eligible studies up to Mar 2012 were identified.

Results

After rigorous searching and screening, 24 case-control studies comprising 3022 cases and 4635 controls were selected for analysis. The overall data failed to indicate the significant associations of CYP2E1 RsaI/PstI polymorphisms with the gastric cancer risk [c2 vs. c1: odds ratio (OR) = 1.06; 95% confidence interval (CI) = 0.88–1.28; c2c2 vs. c1c1: OR = 1.23; 95% CI = 0.78–1.92; c2c2+c1c2 vs. c1c1: OR = 0.93; 95% CI = 0.79–1.10]. Similar results were observed in the subgroup analyses on ethnicity, drinking status, and source of controls. However, in the subgroup analysis on smoking status, a borderline increase in cancer risk was found among long-term smokers (c2c2+c1c2 vs. c1c1: OR = 1.39; 95% CI = 1.00–1.92).

Conclusion

CYP2E1 RsaI/PstI polymorphisms may modify the susceptibility to gastric cancer among individuals who have a smoking history. Large and well-designed studies are needed to confirm this conclusion.     

Coffee Consumption and Risk of Breast Cancer: An Up-To-Date Meta-Analysis

Objectives

This updated meta-analysis was conducted to assess the association between coffee consumption and breast cancer risk.

Methods

We conducted a systematic search updated July 2012 to identify observational studies providing quantitative estimates for breast cancer risk in relation to coffee consumption. Pooled relative risks (RRs) with 95% confidence intervals (CIs) were calculated using a random-effects model, and generalized least square trend estimation was used to assess dose–response relationships.

Results

A total of 26 studies (16 cohort and 10 case–control studies) on coffee intake with 49497 breast cancer cases were included in the meta-analysis. The pooled RR showed a borderline significant influence of highest coffee consumption (RR = 0.96; 95% CI 0.93–1.00), low-to moderate coffee consumption (RR = 0.99; 95% CI 0.95–1.04), or an increment of 2 cups/day of coffee consumption (RR = 0.98; 95% CI 0.97–1.00) on the risk of breast cancer. In stratified analysis, a significant inverse association was observed in ER-negative subgroup. However, no significant association was noted in the others.

Conclusions

Our findings suggest that increased coffee intake is not associated with a significantly reduced risk of breast cancer, but we observe an inverse association in ER-negative subgroup analysis. More large studies are needed to determine subgroups to obtain more valuable data on coffee drinking and breast cancer risk.     

Adiponectin-11377CG Gene Polymorphism and Type 2 Diabetes Mellitus in the Chinese Population: A Meta-Analysis of 6425 Subjects

Background

Although adiponectin −11377CG gene polymorphism is implied to be associated with increased type 2 diabetes mellitus (T2DM) risk, results of individual studies are inconsistent.

Objective and Methods

A meta-analysis consisting of 12 individual studies, including a total of 6425 participants, was carried out in order to investigate the association of adiponectin −11377CG gene polymorphism with T2DM. The pooled odds ratio (OR) and its corresponding confidence interval (CI) at 95% were assessed through the random- or fixed- effect model.

Results

A significant relationship was observed between adiponectin −11377CG gene polymorphism and T2DM under allelic (OR: 1.150, 95% CI: 1.060 to 1.250, P = 0.001), recessive (OR: 1.450, 95% CI: 1.180–1.770, P = 0.0004), dominant (OR: 1.071, 95% CI: 1.013–1.131, P = 0.015), additive (OR: 1.280, 95% CI: 1.090–1.510, P = 0.002), and homozygous genetic models (OR: 1.620, 95% CI: 1.310–1.990, P<0.00001). No significant association was found between them under the heterozygous genetic model (OR: 1.640, 95% CI: 0.850–3.170, P = 0.140).

Conclusions

Adiponectin −11377CG gene polymorphism was significantly associated with T2DM risk susceptibility. G allele carriers are predisposed to T2DM risk.     

Cyclin D1 G870A Polymorphism and Risk of Nasopharyngeal Carcinoma: A Case-Control Study and Meta-Analysis

Background

Cyclin D1 (CCND1) plays a key role in cell cycle regulation. It is a well-established human oncogene which is frequently amplified or overexpressed in cancers. The association between CCND1 G870A polymorphism and cancer risk has been widely assessed. However, a definitive conclusion between CCND1 G870A polymorphism and risk of nasopharyngeal carcinoma (NPC) remains elusive.

Methods

We firstly performed a hospital-based case-control study involving 165 NPC cases and 191 cancer-free controls in central-south China, and then conducted a meta-analysis with six case-control studies to evaluate the association between NPC risk and CCND1 G870A polymorphism.

Results

The case-control study found a significant association between CCND1 G870A polymorphism and NPC risk in various comparison models (AA vs. GG: OR = 2.300, 95% CI 1.089–4.857, p = 0.029; AG vs. GG: OR = 2.832, 95% CI 1.367–5.867, p = 0.005; AA/AG vs. GG: OR = 2.597, 95% CI 1.288–5.237, p = 0.008; AA vs. AG/GG: OR = 0.984, 95% CI 0.638–1.518, p = 0.944). Further meta-analysis showed that there was no significant association between CCND1 G870A polymorphism and NPC risk in overall analysis. In the stratified analysis by race, however, significant associations were only found in Caucasians (for the allele model A vs. G: OR = 0.75, 95% CI 0.59–0.97, p = 0.03; for the co-dominant model AA vs. GG: OR = 0.52, 95% CI 0.32–0.86, p = 0.01; for the dominant model AA/AG vs. GG: OR = 0.49, 95% CI 0.32–0.74, p<0.01; for the recessive model AA vs. AG/GG: OR = 0.90, 95% CI 0.61–1.34, p = 0.60).

Conclusions

A significant association between CCND1 G870A polymorphism and NPC risk was found in the central-southern Chinese population. The meta-analysis indicated that CCND1 G870A polymorphism may contribute to the development of NPC in Caucasians.     

A Common Polymorphism near the ESR1 Gene Is Associated with Risk of Breast Cancer: Evidence from a Case-Control Study and a Meta-Analysis

Background

Genome-wide association studies have reported that a polymorphism near the estrogen receptor gene (ESR1) (rs2046210) is associated with a risk of breast cancer, with the A allele conferring an increased risk. However, considering the controversial results from more recent replicated studies, we conducted a case-control study in an independent Chinese Han population and a meta-analysis to clarify the association of this polymorphism with breast cancer risk.

Method and Findings

A hospital-based case-control study including 461 cases and 537 controls from a Chinese Han population was conducted initially, and this study showed that the rs2046210 A allele was significantly associated with breast cancer risk, with an OR of 1.32 (95% CI  = 1.10–1.59). Subsequently, a meta-analysis integrating the current study and previous publications with a total of 53,379 cases and 55,493 controls was performed to further confirm our findings. Similarly, a significant association between this polymorphism and breast cancer risk was also observed in the overall population especially among Asians, with ORs for per A allele of 1.14 (95% CI  = 1.10–1.18) in the overall population and 1.27 (95% CI  = 1.23–1.31) in the Asian population.

Conclusion

Our results provide strong evidence to support that the common polymorphism near the ESR1 gene, rs2046210, is associated with an increased risk of breast cancer in Asian and European populations but not in Africans, although the biological mechanisms need to be further investigated.     

Matrix Metalloproteinase-9 -1562C/T Promoter Polymorphism Confers Risk for COPD: A Meta-Analysis

Background

The role of matrix metalloproteinase (MMP) gene polymorphisms in the development of chronic obstructive pulmonary disease (COPD) has been reported with inconsistent results. This meta-analysis was performed to assess the association of MMP-1 -1607G/GG and MMP-9 -1562C/T promoter polymorphisms with COPD susceptibility.

Methods

Published case-control studies from Pubmed and China National Knowledge Infrastructure (CNKI) databases were retrieved. Data were extracted and pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated.

Results

A total of fourteen case-control studies were included in this meta-analysis. Pooled effect size showed an association of MMP-9 -1562 C/T with the risk of COPD (dominant model: TT+CT vs CC; OR: 1.46; 95% CI: 1.02–2.08; p = 0.04). However, no correlation with COPD was revealed in MMP-1 -1607G/GG polymorphism. When stratified by ethnicity, results indicated MMP-1 -1607G/GG (recessive model: G/G vs G/GG+GG/GG; OR: 1.20; 95% CI: 1.01–1.44; p = 0.04) and MMP-9 -1562 C/T (dominant model; OR: 1.66; 95% CI: 1.01–2.71; p = 0.04) were correlated with COPD susceptibility among Caucasians and Asians respectively. According to source of controls, signifiant association of MMP-9 -1562 C/T (additive model: T vs C; OR:1.71, 95% CI: 1.42–2.07; p<0.00001, and dominant model; OR: 1.92; 95% CI: 1.34–2.76; p = 0.0004) with COPD susceptibility was revealed in the subgroup with smoker-based controls. However, in the aforementioned risk estimates, only the association of MMP-9 -1562 C/T (additive and dominant models) with the risk of COPD in the subgroup with smoker-based controls persisted significantly after Bonferroni correction for multiple testing. Moreover, after excluding the studies without Hardy–Weinberg equilibrium and/or with small sample size, the pooled results were robust and no publication bias was found in this study.

Conclusion

This meta-analysis suggests, when using healthy smokers as controls, MMP-9 -1562 C/T, but not MMP-1 -1607 G/GG polymorphism is associated with the risk of COPD.     

Passive Smoking Exposure from Partners as a Risk Factor for ER+/PR+ Double Positive Breast Cancer in Never-Smoking Chinese Urban Women: A Hospital-Based Matched Case Control Study

Background

The relationship between passive smoking exposure (PSE) and breast cancer risk is of major interest.

Objective

To evaluate the relationship between PSE from partners and breast cancer risk stratified by hormone-receptor (HR) status in Chinese urban women population.

Design

Hospital-based matched case control study.

Setting

Chinese urban breast cancer patients without current or previous active smoking history in China Medical University 1st Hospital, Liaoning Province, China between Jan 2009 and Nov 2009.

Patients

Each breast cancer patient was matched 1∶1 with healthy controls by gender and age (±2 years) from the same hospital.

Measurements

The authors used unconditional logistic regression analyses to estimate odds ratio for women with PSE from partners and breast cancer risk.

Results

312 pairs were included in the study. Women who endured PSE had significantly increased risk of breast cancer (adjusted OR: 1.46; 95% CI: 1.05–2.03; P = 0.027), comparing with unexposed women. Women who exposed to >5 cigarettes/day also had significant increased risk (adjusted OR: 1.99; 95% CI: 1.28–3.10; P = 0.002), as were women exposed to passive smoke for 16–25 years (adjusted OR: 1.87 95% CI: 1.22–2.86; P = 0.004), and those exposed to > 4 pack-years (adjusted OR: 1.71 95% CI: 1.17–2.50; P = 0.004). Similar trends were significant for estrogen receptor (ER)/progesterone receptor (PR) double positive subgroup(adjusted OR: 1.71; 2.20; 1.99; 1.92, respectively), but not for ER+/PR−, ER−/PR+, or ER−/PR− subgroups.

Limitations

limitations of the hospital-based retrospective study, lack of information on entire lifetime PSE and low statistical power.

Conclusions

Our findings provide further evidence that PSE from partners contributes to increased risk of breast cancer, especially for ER/PR double positive breast cancer, in Chinese urban women.     

Intron 3 Sixteen Base Pairs Duplication Polymorphism of P53 Contributes to Breast Cancer Susceptibility: Evidence from Meta-Analysis

Background

P53 is a tumor suppressor gene and plays important role in the etiology of breast cancer. Intron 3 sixteen-bp duplication polymorphism of p53 has been reported to be associated with breast cancer risk. However, the reported results remain conflicting rather than conclusive.

Methods

A meta-analysis including 19 case-control studies was performed to address this issue. Odds ratios (ORs) with 95% confidence intervals (CIs) were adopted to evaluate the association.

Results

The overall results suggested that the variant genotypes were associated with a significantly increased breast cancer risk (Del/Ins vs Del/Del: OR = 1.18, 95% CI: 1.00–1.40; Ins/Ins vs Del/Del: OR = 1.42, 95% CI = 1.09–1.84; Ins/Ins+Del/Ins vs Del/Del: OR = 1.21, 95% CI = 1.03–1.41). When stratifying by sample size of studies, a significantly elevated risk was also observed among large sample studies (>500 subjects) but not among small sample studies (≤500 subjects).

Conclusion

These results suggested that the 16-bp duplication polymorphism of p53 may contribute to susceptibility to breast cancer. Additional well-designed large studies were required to validate this association in different populations.     

Association of GSTM1 Null Allele with Prostate Cancer Risk: Evidence from 36 Case-Control Studies

Background

Glutathione S-transferase M1 (GSTM1) is thought to be involved in detoxifying several carcinogens and may play a vital role in tumorigenesis. Numerous studies have evaluated the association between GSTM1 null/present polymorphism and risk of prostate cancer (PCa). However, the results remain inconsistent. To derive a more precise estimation, we performed a meta-analysis.

Methodology/Principal Findings

A comprehensive search was conducted to identify all eligible case-control studies. We used odds ratios (ORs) with 95% confidence intervals (CIs) to assess the strength of the association. The overall association was significant (OR = 1.28, 95% CI: 1.11–1.48, P = 0.001). Moreover, subgroup analyses showed GSTM1 null genotype significantly associated with PCa risk among Asians (OR = 1.35, 95% CI: 1.03–1.78, P = 0.03) but not among Caucasians (OR = 1.12, 95% CI: 0.96–1.31, P = 0.16). In addition, we did not find that smoking modified the genotype effect on the risk of PCa.

Conclusions/Significance

The present meta-analysis suggested that GSTM1 null allele was a low-penetrant risk factor for PCa among Asians.     

Functional Promoter -94 ins/del ATTG Polymorphism in NFKB1 Gene Is Associated with Bladder Cancer Risk in a Chinese Population

Background

A functional -94 insertion/deletion polymorphism (rs28362491) in the promoter of the NFKB1 gene was reported to influence NFKB1 expression and confer susceptibility to different types of cancer. This study aims to determine whether the polymorphism is associated with risk of bladder cancer.

Materials and methods

TaqMan assay was used to determine genotype among 609 cases and 640 controls in a Chinese population. Logistic regression was used to assess the association between the polymorphism and bladder cancer risk, and quantitative real-time polymerase chain reaction was used to determine NFKB1 mRNA expression.

Results

Compared with the ins/ins/ins/del genotypes, the del/del genotype was associated with a significantly increased risk of bladder cancer [adjusted odd ratio (OR)  = 1.92, 95% confidence interval (CI)  = 1.42–2.59]. The increased risk was more prominent among subjects over 65 years old (OR  = 2.37, 95% CI  = 1.52–3.70), male subjects (OR  = 1.97, 95% CI = 1.40–2.79) and subjects with self-reported family history of cancer (OR  = 3.59, 95% CI  = 1.19–10.9). Furthermore, the polymorphism was associated with a higher risk of developing non-muscle invasive bladder cancer (OR  = 2.07, 95% CI  = 1.51–2.85), grade 1 bladder cancer (OR  = 2.40, 95% CI  = 1.68–3.43), single tumor bladder cancer (OR  = 2.04, 95% CI  = 1.48–2.82) and smaller tumor size bladder cancer (OR  = 2.10, 95% CI  = 1.51–2.92). The expression of NFKB1 mRNA in bladder cancer tissues with homozygous insertion genotype was higher than that with deletion allele.

Conclusions

In conclusion, the -94 ins/del ATTG polymorphism in NFKB1 promoter may contribute to the etiology of bladder cancer in the Chinese population.     

The Genetics of Primary Haemorrhagic Stroke,Subarachnoid Haemorrhage and Ruptured Intracranial Aneurysms in Adults

Background

The genetic basis of haemorrhagic stroke has proved difficult to unravel, partly hampered by the small numbers of subjects in any single study. A meta-analysis of all candidate gene association studies of haemorrhagic stroke (including ruptured subarachnoid haemorrhage and amyloid angiopathy-related haemorrhage) was performed, allowing more reliable estimates of risk.

Methods

A systematic review and meta-analysis of all genetic studies in haemorrhagic stroke was conducted. Electronic databases were searched until and including March 2007 for any candidate gene in haemorrhagic stroke. Odds ratio (OR) and 95% confidence intervals (CI) were determined for each gene disease association using fixed and random effect models.

Results

Our meta-analyses included 6,359 cases and 13,805 controls derived from 55 case-control studies, which included 12 genes (13 polymorphisms). Statistically significant associations with haemorrhagic stroke were identified for those homozygous for the ACE/I allele (OR, 1.48; 95% CI, 1.20–1.83; p = 0.0003) and for the 5G allele in the SERPINE1 4G/5G polymorphism (OR, 1.42; 95% CI, 1.03–1.96; p = 0.03). In addition, both &b.epsi;2 and &b.epsi;4 alleles of APOE were significantly associated with lobar haemorrhage (OR, 1.81; 95% CI, 1.26–2.62; p = 0.002 and OR, 1.49; 95% 1.08–2.05; p = 0.01 respectively). Furthermore, a significant protective association against haemorrhagic stroke was found for the factor V Leiden mutation (OR, 0.30; 95% CI, 0.10–0.87; p = 0.03).

Conclusion

Our data suggests a genetic contribution to some types of haemorrhagic stroke, with no overall responsible single gene but rather supporting a polygenic aetiology . However, the evidence base is smaller compared to ischaemic stroke. Importantly, for several alleles previously found to be associated with protection from ischaemic stroke, there was a trend towards an increased risk of haemorrhagic stroke.     

Tea and Coffee Consumption and Risk of Laryngeal Cancer: A Systematic Review Meta-Analysis

Background

Tea and coffee are the most commonly consumed beverages in the worldwide. The relationship between tea and coffee consumption on the risk of laryngeal cancer was still unclear.

Methods

Relevant studies were identified by searching electronic database (Medline and EMBASE) and reviewing the reference lists of relevant articles until Oct. 2013. Observational studies that reported RRs and 95% CIs for the link of tea and coffee consumption on the risk of laryngeal cancer were eligible. A meta-analysis was obtained to combine study-specific RRs with a random-effects model.

Results

A total of 2,803 cases and 503,234 controls in 10 independent studies were identified. The overall analysis of all 10 studies, including the case-control and cohort studies, found that tea drinking was not associated with laryngeal carcinoma (RR = 1.03; 95% CI: 0.66–1.61). However, coffee consumption was significantly associated with the laryngeal carcinoma (RR = 1.47; 95% CI: 1.03–2.11). A dose-response relationship between coffee intake and laryngeal carcinoma was detected; however, no evidence of dose-response link between tea consumption and laryngeal carcinoma risk was detected.

Conclusions

The results from this meta-analysis of observational studies demonstrate that coffee consumption would increase the laryngeal cancer risk, while tea intake was not associated with risk of laryngeal carcinoma.